214例HIV/AIDS病人的HAART不良反应及换药原因分析

目的探讨艾滋病病毒（HIV）感染者/艾滋病（AIDS）病人（简称HIV/AIDS病人）高效抗反转录病毒治疗（HAART）的不良反应及换药原因。为保证HAART合理用药及用药安全提供依据。方法全部病人均使用国家免费艾滋病HAART药物,按照国家免费艾滋病抗病毒药物治疗手册要求,全部病例均在HAART后1、2、3、6、9、12个月随访1次,统计病人不良反应及换药原因,数据分析用SPSS 19.0软件处理,以P〈0.05为差异有统计学意义。结果 95例病人中90例出现抗病毒药物不良反应、3例一线治疗失败、2例因药物配伍禁忌更换抗病毒药物。其中90例病人因AZT、NVP、D4T不良反应更换抗病毒药物。另有3例初始HAART方案包含EFV的病人,出现神经系统症状,均自行缓解,未更换药物。将初始HAART方案包含AZT、NVP、D4T的病例分为未换药组和换药组,将两组病人的基线CD＋4T淋巴细胞（简称CD4细胞）计数值进行统计学比较,差异无统计学意义。结论HAART的主要换药原因为抗病毒药物不良反应。在包含AZT、D4T、NVP的HAART方案中,治疗前3个月着重监测AZT、NVP的不良反应,治疗6个月后着重监测D4T的不良反应,且不良反应的出现与基线CD4细胞计数无关。同时须及早发现耐药,并须掌握药物配伍禁忌。     

艾滋病抗病毒治疗的新认识

高效抗逆转录病毒疗法（HAART）是把不同作用机制的抗HIV药物组合使用,从而达到稳定、持久地抑制HIV效果（如抑制患者血液中的HIVRNA水平使之低于检测下限）,是目前治疗艾滋病最根本的方法。HAART自1996年问世以来,已使艾滋病从1种致命性疾病变成1种可以治疗的慢性疾病。随着新的抗HIV药物的出现以及对疗法本身（药物组合、临床疗效、不良反应、长期获益等）的不断探索,每年均有对艾滋病抗病毒治疗的新认识。     

抗艾滋病病毒药物的肝损伤

高效抗逆转录病毒治疗（HAART）已经明显地降低了艾滋病相关的发病率和死亡率。但是，接受HAART治疗的患者通常在遭受药物副作用的困扰。因此，HIV感染治疗已经成为持续HIV病毒抑制与药物毒性危险性之间复杂的平衡行为。HAART的毒性作用之一是肝毒性，其可造成HIV患者的治疗中断、亚临床肝炎，甚至出现致死性肝衰竭。目前，HAART导致肝毒性的机理尚不清楚。本文就HAART导致肝毒性的发病机制、发生率、临床影响、危险因素以及临床处理作一综述。     

艾滋病抗病毒治疗新药的研究进展

高效联合抗逆转录病毒治疗(HAART)能够阻断人类免疫缺陷病毒(HIV)的复制,恢复艾滋病(AIDS)病人的免疫功能,是目前治疗艾滋病的唯一有效手段.近年来艾滋病抗病毒治疗新药研究取得较大进展,有多种新的抗HIV药物为艾滋病的临床治疗提供更多选择,其中既有针对逆转录酶和蛋白酶的新型抑制剂,也包括对整合酶、辅助受体等新靶点的药物.该文针对新近获准应用于临床和有望进入临床的新药作一综述.     

中国农村地区开展高效抗逆转录病毒治疗药物不良反应管理策略的初步探讨

高效抗逆转录病毒治疗(Highly Active Azati-retroviral Therapy,HAART)能够有效抑制人类免疫缺陷病毒Ⅰ型(HIV-1)的复制,延缓疾病的临床进展,改善患者的生活质量,大大降低了艾滋病的发病率和死亡率.由于中国大部分HIV/AIDS患者都生活在医疗条件有限的农村地区,基层医疗设备、药物供应及医务人员的技术水平均有限,对农村地区开展HAART更是缺乏经验,由抗逆转录病毒(ARV)药物引起的不良反应颇为常见,因此在治疗过程中,监测和管理因ARV药物引起的不良反应是保证治疗安全性和有效性的关键.该文详细介绍了临床试验研究现场的相关工作经验,探讨其中可以推广并用于国家免费HAART工作的方法和策略.     

抗逆转录病毒治疗新药物的选择（上）——Paul E．Sax，MD答Medscape网记者问

10年前高活性抗逆转录病毒治疗（HAART）引入临床，而且自那以后不断取得了基础治疗的进步，新的药物和治疗策略不断出现，改善了HIV病人的预后和生活质量。在美国科罗拉多州丹佛召开的第13届逆转录病毒和机会性感染（CROI）大会上，Medscape网记者就新的抗逆转录病毒药物和药物联合治疗以及新的化合物治疗HIV感染与专家进行了探讨。     

抗HIV药物临床耐药研究进展

高效抗反转录病毒治疗(HAART)开展以来,控制了艾滋病病毒/艾滋病(HIV/AIDS)及相关疾病的进程,延长了患者的生存时间。然而由于HIV有高度的遗传变异性,同时在药物选择压力的作用下,HIV可逐渐对一种或几种药物产生耐药。随着HAART时间的延长及治疗人数的增多,HAART在目前及今后的治疗中面临HIV耐药的考验。对HIV临床耐药进行总结分析,有利于合理开展HAART治疗并减少耐药病毒株的出现及传播。     

高效抗反转录病毒治疗相关性脂肪代谢综合征

自1996年高效抗反转录病毒治疗(HAART)应用于临床以来,艾滋病的发病率和死亡率已经大大降低。但HAART治疗需长期或终身服药,因此,药物的毒副作用容易导致患者的依从性下降。其中脂肪代谢综合征就是HAART用药过程中的一个比较常见的远期不良反应之一。HAART药物中与脂肪代谢有关的主要是蛋白酶抑制剂(PIs)和核苷类逆转录酶抑制剂(NRTIs),可以引起各种代谢异常和内分泌紊乱综合征。其具体的发病机制目前尚不清楚。本文就脂肪代谢综合征的发病机制、检测及治疗进行了阐述。     

天津市高效抗逆转录病毒治疗艾滋病临床观察

目的评价天津市艾滋病（AIDS）初治患者,应用高效抗逆转录病毒治疗（HAART）的疗效、安全性和预后。方法将在天津市传染病医院就诊的62例AIDS患者,随机分成治疗组（45例）及对照组（17例）;治疗组应用一线HAART方案：AZT／D4T＋3TC＋NVP／EFV。观察两组患者的临床表现、免疫功能变化及预后。结果（1）HAART治疗组与对照组患者基线CD4 T细胞计数差异无统计学意义（P〉0．5）;治疗组的45例患者,HAART前CD4 T细胞计数均值为73／μl;HAART后3、6、12个月时分别为120／μl（39例）、139．5／μl（30例）和200／μl（22例）。（2）治疗组患者应用HAART后,机会性感染、肿瘤的发生率和病死率分别为40％和4．44％,均显著低于对照组的88．24％和47．06％（P〈0．01）。（3）初治患者一线HAART治疗的有效率为95．55%（43／45）,有17．78％（8／45）的患者因药物不良反应而调整HAART方案。结论天津市AIDS患者对一线HAART有较好的疗效,随着HAART疗程的延长,免疫功能得到恢复并改善了预后,存在药物不良反应和资源有限等问题。     

抗逆转录病毒治疗(HARRT)相关肝脏毒性的临床综合征及结局

治疗人类免疫缺陷病毒（HIV）感染常需解释和处理丙氨酸氨基转移酶（ALT）升高。已陆续发现了与高效抗逆转录病毒治疗（HAART）相关的肝脏问题。新的抗逆转录病毒药物已获批准,而其肝脏安全性的信息有限。     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.